INCREASE OF METALLOPROTEINASES (MMPs) ACTIVITY AND MIGRATORY ABILITY OF THYROID TUMOR CELLS INDUCED BY TUMOR CELL-FIBROBLAST INTERACTION

DELLA VEDOVA AB; REMEDI MM; GILARDONI MG; MASINI-REPISO AM; PELLIZAS CG; DONADIO AC

Florianópolis

Congreso; XV Latin American Thyroid Congress; 2013

Background: Carcinomas comprise tumor and stromal cells like fibroblasts (Fb), immune and endothelial cells, immersed in the extracellular matrix (ECM).Tumor-stroma cross-talk influences tumor behaviour. Proteases like MMPs induce ECM degradation and epithelial-mesenchymal transition. Fb confer growth-promoting advantage to thyroid carcinoma cells. The role of thyroid tumor-Fb interaction in the invasive and migratory ability of tumor cells remain unknown. Objectives: To analyse MMPs expression and thyroid tumor cell migration induced by tumor-Fb interaction. Methods: Thyroid carcinoma papillary (TPC-1), anaplastic (8505c) and normal thyroid (N-ThyOri) cell lines were cultured with (co-cultured) or without normal Fb. MMP2 and MMP9 expression was analyzed in culture supernatants (Conditioned-Media, CMs) by zymography and in cultured cells by immunofluorescence. Tumor cell migration was evaluated by the wound healing assay and the presence of lamellipodia/filopodia, as a signal of migratory phenotype (rhodamine-phalloidin staining). Results: An increase in MMP2 and MMP9 expression alongside with higher levels of active MMP2 was observed in CMs from TPC-1-Fb and 8505c-Fb co-cultures. MMP9 protein staining increased in Fb co-cultured with tumor cells while MMP2 displayed a dotted pattern in Fb plasmatic membrane. No significant MMPs changes were observed in N-ThyOri-Fb co-cultures. TPC-1 and 8505c cells with lamellipodia/filopodia increased after Fb CMs as well as 8505c cells after tumor-Fb CMs incubation. A significant wound healing closure was observed only in 8505c cells, after incubation with Fb or 8505c-Fb CMs. Conclusions: Tumor cell-Fb interaction increased MMP2 and MMP9 expression and activity. Fb soluble factors could be relevant for the promotion of thyroid tumor cell invasive phenotypes.